New & Noteworthy

Parthenogenesis is one of the cooler things in biology. When a female Komodo dragon can’t find a mate, her eggs simply double their DNA and voila, a whole litter of female Komodo dragons is born. (Interestingly, they aren’t clones of mom…)

Now, this doesn’t work in mammals like us (curse you imprinting!), but something similar can happen in yeast. Given the right conditions and the right mutations, yeast can go from haploid to diploid without all that messy mating.

In a new study out in GENETICS, Schladebeck and Mösch uncover the newest mutation to be shown to cause whole genome duplication (WGD) in haploid Saccharomyces cerevisiae: the whi3 deletion. And this mutant is no slouch…the haploid will go diploid in no time flat if given the right conditions.

Schladebeck and Mösch looked at the stability of the haploid state of the whi3 mutant in both minimal and rich media, either in liquid culture or on solid agar. They generated fresh whi3 deletion strains and then followed them in each of these growth conditions for 72 days, passaging them every two days.

What they found was that the haploid state was actually pretty stable in liquid culture using minimal media. They found very few diploid cells after 72 days. The same was not true for the other growth conditions.

On solid minimal media and liquid rich medium, there was a complete switch after 72 days. And on solid rich medium, the cells were all diploid after only 14 days. Genome duplication appeared to stop at the diploid level though. Even after 72 days on solid rich media there was no sign of tetraploids.

The authors next set out to figure out why deleting WHI3 had such a profound impact on haploid stability. They have not yet figured out everything that is going on, but they did uncover some interesting clues.

First they looked at the protein Nip100p. They already knew that NIP100 interacted genetically with WHI3, and that a nip100 deletion mutation affected chromatid separation. They found that Nip100p levels were significantly reduced when WHI3 was deleted, and even more so when the whi3 mutant strain was grown on solid rich medium. These are the conditions that most favored the transition from haploid to diploid. This suggests that NIP100 might be a key player in maintaining the haploid state.

The authors also compared transcriptional profiles of the wild type haploid strain, the whi3 deletion in a haploid background, and the whi3 homozygous mutant diploid. One of the findings from these experiments was that most of the genes involved in the yeast cohesion complex were upregulated in the absence of WHI3. Since this complex is required for sister chromatid cohesion, the idea would be that inefficient separation of chromatids in the whi3 mutant would increase the rate of whole genome duplication.

One of the as yet unexplained aspects of all of this is why the diploid state remains stable. There was no difference between the haploid and diploid deletion strains with regard to either Nip100p levels or transcription of cohesion-relate4d genes – the cohesins were upregulated in both and Nip100p was reduced in both.

One idea Schladebeck and Mösch put forth is that the diploid state isn’t inherently stable in this mutant. Instead, they do not see tetraploids simply because tetraploids have decreased viability. They appear but are quickly outcompeted by their diploid sisters.

The discovery about WHI3’s role in controlling ploidy is just one aspect of this new study. The authors also found important new information about the central regulatory role of WHI3 in cell division and biofilm formation.

The finding about ploidy control is important because maintaining haploid and diploid status is obviously a big deal: you don’t want to switch willy nilly from one to the other. And many pathogenic fungi, such as Candida albicans, change the organization of their genomes to adapt to changing growth conditions in their human hosts. They have WHI3 homologs, so these results could lead to better ways to cure fungal infections. Just one more example of how basic research can lead scientists to stumble on unexpected but ultimately important results…